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The longitudinal decline in lung function in swine barn workers has been linked to air con-taminants [22] and a dose-response relationship exists between decline in lung function and end

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and Toxicology

Open Access

Review

Pulmonary effects of exposure to pig barn air

Chandrashekhar Charavaryamath and Baljit Singh*

Address: Department of Veterinary Biomedical Sciences and Immunology Research Group, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada

Email: Chandrashekhar Charavaryamath - c.chandru@usask.ca; Baljit Singh* - baljit.singh@usask.ca

* Corresponding author

Abstract

Swine production has undergone rapid transformation from family owned operation to a large scale

industrial enterprise Since increasing number of pigs are reared on a large scale in confined

buildings, some of the swine barn workers may be employed to work eight hours per day Swine

barn workers suffer from higher incidences of impaired air flow and lung inflammation, which is

attributed to high intensity and interrupted exposures to pig barn air The air in these barns

contains gases, dust, microbes and endotoxin with endotoxin being the major suspect as the cause

of lung dysfunction This review attempts to describe the current state of knowledge of incidences

and mechanisms of pulmonary dysfunction following exposure to the barn air

Changing face of pig industry in Canada

Canada is among the top five pork exporters of the world

with a total pork export of 970,000 tons in the year 2004,

which translates into cash receipts of $4.2 billion in the

year 2004 representing a 25% increase over the year 2003

In 2005, Canada had 14.9 million hogs which is an

increase of 1.7% over the previous year and the pork

export is expected to grow by 2% [1,2] Currently, pork

sector accounts for 30% of total livestock shipments and

for 10% of all farm cash receipts in Canadian farm

econ-omy Further, swine farming has provided employment to

10,790 people in Canada [3] Therefore, swine

produc-tion is a major component of Canada's agricultural

econ-omy Although the number of pigs has increased but the

number of farms has shown a decline to indicate fewer

people are working longer shifts on the farms Now a

days, small family operated pig farms are making way for

large scale facilities where thousands of pigs are raised in

a single facility [4] Large pig production operations

require many full time workers who work 8 hour/day and

5 days/week and thus experience high intensity

inter-rupted exposures to the barn air [5,6] However, still many workers may work only a few hours every day inside a pig barn The barn air is very complex and contains organic dust, plant materials (pollen grains, feed grains, hay and silage), animal origin materials (swine dander, hair, urine and pig proteins), microbial components (mite or their parts, bacteria, endotoxin, (1–3) β-D-glucan and fungal spores) and a number of gases such as ammonia, carbon dioxide, hydrogen sulphide and methane [7-9] Therefore, although modern barns appear cleaner, the air inside these barns still carries toxic molecules which are harmful

to the workers [10]

Clinical symptoms

Exposure to the toxic molecules in the barn air is a risk fac-tor for the development of chronic respirafac-tory symptoms and lung dysfunction [11] Respiratory diseases in agricul-tural farmers are one of the earliest recognized occupa-tional hazards [12] Among the agriculture workers, swine farmers report higher prevalence of occupational respira-tory symptoms than in other farmers [13] Exposed

work-Published: 06 June 2006

Journal of Occupational Medicine and Toxicology 2006, 1:10 doi:10.1186/1745-6673-1-10

Received: 06 February 2006 Accepted: 06 June 2006 This article is available from: http://www.occup-med.com/content/1/1/10

© 2006 Charavaryamath and Singh; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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ers report significantly higher frequencies of respiratory

symptoms, chest illness, cold and pneumonia [7,14] The

severity of respiratory symptoms in the workers increases

during the winter due to the reduced ventilation and is

also related to the number of working hours [15]

Previous studies have recorded reductions in expired flow

rates in barn workers [11][16-19] Further, barn workers

also exhibit increased airway responsiveness and airway

inflammation [20,21] The longitudinal decline in lung

function in swine barn workers has been linked to air

con-taminants [22] and a dose-response relationship exists

between decline in lung function and endotoxin and

ammonia levels in the barn air [17] Exposure to the barn

organic dust causes airway inflammation and increased

airway resistance both in humans and animal models

apart from contributing to the exacerbation of asthma

[23-27] These observations show that the barn air

con-tains toxic molecules which induce lung dysfunction in

pig barn workers

Effects of acute single exposure to the swine

barn air: human studies

To better understand the negative effects of exposure to

swine barn air, many researchers have exposed nạve,

healthy volunteers to the swine barn air for a short period

of time (2–5 hours, once) This study model mimics the

lung response of new workers following first exposure to

the swine barn air Single two-five hours of exposure of

nạve, healthy volunteers to swine barn air is shown to

induce bronchial responsiveness [28], fever, malaise and

drowsiness [21] Across the shift change in lung function

during exposure is an important predictor of longitudinal

changes in lung function in swine confinement workers

[29] Further, a 75-fold increase in neutrophils, a

two-three fold increase in mononuclear cells and a significant

increase in eosinophils, fibronectin and albumin levels in

bronchoalveolar lavage fluid (BALF) [21] and levels of

IL-1β, IL-1 receptor antagonist, IL-6 and TNF-α increased in

the serum of the exposed nạve volunteers The changes in

IL-1 receptor antagonist levels correlated with changes in

FEV1, bronchial responsiveness, oral temperature and

white blood cell count while IL-1β levels correlated with

oral temperature [30] Further, it is shown that, a single

exposure to barn air also caused thickening of nasal

mucosa, increased numbers of neutrophils in nasal lavage

and BALF, increased numbers of macrophages,

lym-phocytes, eosinophils and the levels of IL-8 in the BALF

[31,10] Interestingly, levels of IL-8, a potent

chemoat-tractant for neutrophils, correlated with increase in

neu-trophils in the nasal lavage fluid [31] It is obvious that

single exposure to the barn air can activate an

inflamma-tory response in human lungs

Animal exposure studies

Although data from studies involving human volunteers has shown induction of lung inflammation following exposure to the barn air, animal studies are critically needed to better understand cell and molecular changes

So far, there have been very few animal model studies to map the mechanisms of barn air-induced lung dysfunc-tion For example, rabbits and guinea pigs maintained for

12 months in a confined nursery-grower unit showed dif-fuse interstitial histiocytic pneumonia, epithelial hyper-plasia and metahyper-plasia of tracheal and nasal turbinates, with sub mucosal infiltration of plasma cells and heter-ophils [32] Interestingly, blood from these test animals contained serum precipitins to dust extract from the swine confinement building [32]

To mimic the work schedule at modern pig barns, we exposed Sprague-Dawley rats to pig barn air for a period

of 8 hours/day for one day, 5 days or 20 days The expo-sures were interrupted for 2 days after each 5 days of 8 hour/day exposure and rats were kept in clean air during this interruption Rats exposed to the swine barn air for one or five times showed increase in airway hyperrespon-siveness compared to those exposed 20 times or controls Lungs from all the three exposed groups (one, five and 20 day) were inflamed with recruitment of neutrophils and eosinophils in five and 20 day exposed groups [33] These responses are similar to those observed in human volun-teers exposed to the barn air for 3–5 hours [28,34,35] Interestingly, airway reactivity in rats following 20 expo-sures was not different compared to the controls to sug-gest physiological adaptation to the pig barn air Similarly, following single exposure to the barn air, swine farmers only show minor alterations compared to nạve volunteers to suggests adaptation [36,37] It is possible that adaptation in animal models may be induced follow-ing exposures shorter than 8 hours

Because we found high concentrations of endotoxin in the barn air, it may be central protagonist in initiating lung inflammation in the exposed animals These data show that rat lung responses to the barn air are similar to those

in humans and that rat may be a reliable model to simu-late lung dysfunction in humans following exposure to the barn air [33]

In vitro studies on the effects of swine barn dust

Several researchers have shown the inflammatory

poten-tial of swine barn dust or air in many in vitro experiments

[38-40] These in vitro studies are a valuable tool to under-stand the effects of swine barn air or dust on a variety of lung cells These studies provide an opportunity to control various variables to facilitate identification of cellular and molecular pathways that regulate response to swine barn air Swine dust induces release of IL-8 in normal human

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bronchial epithelial cells, human pulmonary epithelial

carcinoma cell line (A549) and in human alveolar

macro-phages [38] Swine dust is almost as potent as

lipopolysac-charides in stimulating cytokine release from alveolar

macrophages in vitro [39] Recent data showed that swine

barn dust activates protein kinase C to induce secretion of

IL-8 and IL-6 from airway epithelial cells and promotes

adhesion of lymphocytes through upregulation of

ICAM-1 [40,4ICAM-1] Swine barn dust can also directly activate

T-lym-phocytes [42] These data show importance of performing

in vitro studies along with human and experimental

ani-mal investigations to further our understanding of lung

responses to pig barn air

Conclusion and future studies

The data from animal and human studies show that barn

air can induce lung dysfunction Recent data from animal

studies and from in vitro studies have started to elucidate

mechanisms of lung dysfunction induced following

expo-sure to the barn air However, many questions remain

unanswered One of the central questions relates to

pre-cise and relative contributions of various toxic molecules

in the barn air to lung dysfunction The endotoxin is the

foremost toxic agent in the barn air The role of endotoxin

in barn air induced lung dysfunction can be assessed

through the use of mice that lack a functional Toll-like

receptor-4 Second logical experiment is the physical and

biochemical characterization of the dust particles in the

barn air Specifically, we need to know if the barn air

con-tains dust particles which are less then 100 nm in size

because particles of this size are believed to provoke a

vig-orous cardiopulmonary response [43,44] The

biochemi-cal characterization of the particles would reveal if

particles are used as Trojan horse to carry endotoxins and

other toxic molecules into the lungs

Competing interests

The authors declare that they have no competing interests

Authors' contributions

Both the authors contributed equally in the preparation of

this review

Acknowledgements

The work done in the authors' laboratory was supported through grants

from Saskatchewan Lung Association and Natural Sciences and Engineering

Research Council of Canada to Dr Singh Dr Charavaryamath is supported

through Graduate Merit Scholarship from University of Saskatchewan

(2002–2004) and a scholarship from the CIHR Strategic Training Program

in Public Health and the Agricultural Rural Ecosystem (PHARE) and Partner

Institutes including the Institute of Cancer Research, Institute of

Circula-tory and RespiraCircula-tory Health, Institute of Infection and Immunity, Institute

of Population and Public Health and the University of Saskatchewan We

regret that due to space constraints we may not have cited a few worthy

publications.

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